Gilles de la Tourette Syndrome (GTS) is a common, highly heritable, childhood-onset neuropsychiatric disorder that is characterized by marked clinical heterogeneity and variable response to existing treatments. The purpose of this Mentored Career Development Award in Patient-Oriented Research (K23) is to train the candidate in statistical, genetic and clinical epidemiologic methods so that he can become an independent investigator in translational, clinical genetic research. The research plan consists of: 1) a clinical phenotyping aim using item-level exploratory and confirmatory factor analysis to define homogeneous, symptom-based GTS subphenotypes that may more adequately capture the diverse clinical features of the disease; 2) a secondary analysis of a GTS genome-wide association study (GWAS) using the heritiable subphenotypes in Aim 1 to identify GTS susceptibility alleles; 3) a training aim in which the candidate will participate in selected aspects of his co-mentor's pilot, randomized controlled trial of combined behavioral therapy and pharmacotherapy for GTS to acquire the skills and experience necessary to conduct future GTS clinical trials that can incorporate phenotypic and genetic predictors of treatment response. ' The proposed study will be conducted at Massachusetts General Hospital under the mentorship of David Pauls, Ph.D., an expert in GTS phenotypic and genetic research, and the co-mentorship of Sabine Wilhelm, Ph.D., an expert in GTS treatment research. A group of nationally-recognized mentors and consultants, both local and external, will provide additional mentoring in specialized areas of expertise relevant to each research and training goal. The career development plan includes a didactic component combining coursework at the Harvard School of Public Health and Harvard University Department of Psychology with guided tutorials in study design, biostatistics, statistical genetics, and clinical thals methods. This integrated research and training program will lay the groundwork for future, multi-center pharmacogenetic studies of GTS treatment response and will prepare the candidate to submit an R01 application for translational genetic studies of GTS and related disorders. RELEVANCE (See instructions): This research aims to define more precise disease definitions for GTS, to identify GTS susceptibility genes, and to train the investigator in clinical trials methods so that he can apply these novel disease definitions and genes to future GTS treatment studies. Completion of this study will train the investigator to become a leader in translational research aimed at developing personalized treatments for GTS patients.